I have been asking myself this question. While I am trying to contribute to the success of drug discovery within a big pharma company, I truly wonder. We are faced with more and more processes that originate from people who focus on production environments and standards. It gets increasingly more difficult to explain and educate higher management about the essential differences between research and development or production: For example, it can be alright to have standard rules for administering computers (e.g. removal of administrator rights, use of approved software, etc., to cut costs), but part of research is that a scientist needs to be able to try new programs or algorithms to assess whether they improve the quality of his or her experimental results. Big pharma companies that are serious about internal research need to make sure that they create and maintain a different working environment for scientists in research in contrast to colleagues who work in much more standardized (and understandably more controlled) environments such as production. This is especially true for areas of research that involve the generation of lots of data such as imaging, sequencing, molecular profiling, etc.

Furthermore, it will be the pharma companies who will create some level of academic freedom within their research organizations who will succeed. Freedom for creativity / creative thoughts and experiments are the true basis of innovation. Innovation can only take place where it is possible to be creative and try out creative ideas. Scientists in pharma should watch out that their brains are not increasingly focused on rational thinking (writing reports, answering emails, attending meetings, etc.) while cutting shorter and shorter the time and freedom they have for creative thinking.

In an article just published in the New England Journal of Medicine the authors Andreas Diacon et al. report an interim analysis of data obtained during the first stage of an ongoing two-stage Phase II trial with TMC207/R207910. The clinical trial focusses on patients with multidrug resistant tuberculosis (MDR-TB): patients are randomized into 2 groups receiving either a placebo or TMC207/R207910 together with a background second-line antituberculosis regimen of five other antibiotics (kanamycin, ofloxacin, ethionamide, pyrazinamide, and cycloserine or terizidone).

The data reported in the article looks at the conversion of sputum cultures from positive to negative over 8 weeks of treatment. Sputum samples were taken at weekly intervals to test for growth of Mycobacterium tuberculosis in liquid culture. Here a significant increase in the proportion of patients that showed a negative sputum culture (no growth of Mycobacterium tuberculosis in liquid culture) was seen: 48% versus 9% in the placebo group. The time it took for those patients to achieve negative sputum culture was shorter compared to just the background treatment. The number of colony-forming units declined more quickly in comparison to the placebo group.

Some numbers: 47 patients with newly diagnosed MDR-TB were randomized to receive either one of the two treatments. TMC207/R207910 was given at 400 mg daily for 2 weeks and 200 mg three times per week for 6 weeks. The placebo group included 24 patients and the TMC207/R207910 group included 23 patients. 6 patients stopped the treatment prematurely - 3 in each group.

Besides the promising interim data that encourages my hopes for finally bringing a new drug against Mycobacterium tuberculosis to patients, it is also very exciting from a scientific point of view: if the clincal trial were to continue successfully, the ATP synthase of the bacterium which we identified as the target of TMC207/R207910 will be established as a viable target for the development of antibiotics. The authors of the study write in the discussion of the article: "In conclusion, the safety and efficacy findings from this study clinically validate ATP synthase as a new target for antituberculosis therapy."

The abstract of the article plus links to the full version of the article can be found here. Our original Science paper identifying the ATP synthase as the target of TMC207/R207910 can be found here.